Exploring the Role of Cerebrospinal Fluid and Serum Mid-Regional Pro-Adrenomedullin in Tick-Borne Encephalitis: A Pilot Study.

Background

Adrenomedullin (ADM) is a multifunctional peptide with vasoregulatory, antimicrobial, and anti-inflammatory properties. Its stable fragment, mid-regional pro-adrenomedullin (MR-proADM), is a validated biomarker in sepsis and systemic infections, but its role in viral neuroinfections remains unexplored. Tick-borne encephalitis (TBE), caused by the tick-borne encephalitis virus (TBEV), is a major viral infection of the central nervous system (CNS) associated with long-term neurological sequelae. This study aimed to assess MR-proADM levels in cerebrospinal fluid (CSF) and serum of patients with TBE and to evaluate their diagnostic utility and pathophysiological significance.

Methods

This retrospective observational study included 20 patients with confirmed TBE and 14 non-infectious neurological controls. MR-proADM concentrations were measured in paired CSF and serum samples using an ELISA assay. Statistical analyses included group comparisons (Mann-Whitney U test), correlation analyses (Spearman's r), and receiver operating characteristic (ROC) curve evaluation.

Results

Serum MR-proADM levels at baseline (SER1) were significantly lower in TBE patients compared with controls (p = 0.0197). The CSF/serum MR-proADM ratio differed significantly between groups (p = 0.0063) and showed the best diagnostic performance (AUC = 0.816, 95% CI 0.63-0.93; sensitivity 79%, specificity 80%). MR-proADM concentrations in CSF correlated with total CSF protein (r = 0.53), suggesting an association with blood-CSF barrier dysfunction. Strong reproducibility was observed for serum MR-proADM between sampling points (r = 0.83).

Conclusions

MR-proADM levels in CSF and serum are altered in patients with TBE, indicating its potential as a biomarker of CNS infection and inflammation. The CSF/serum MR-proADM ratio may serve as a sensitive indicator of blood-CSF barrier involvement, while decreased serum levels may reflect impaired systemic neuroprotective response. These findings highlight a possible role of ADM in neuroimmune regulation during viral encephalitis and warrant validation in larger prospective studies.